Susana N Banerjee1, Monica Tang2, Rachel L O'Connell2, Katrin Sjoquist2, Andrew R Clamp3, David Millan4, Steven Nottley4, Rosemary Lord5, Vinod Menon Mullassery6, Marcia Hall7, Charlie Gourley8, Tony Bonaventura9, Jeffrey C Goh10, Peter Sykes11, Peter T Grant12, Orla McNally13, Laura Alexander14, Caroline Kelly14, Karen Carty14, Laura Divers14, N Bradshaw2, Richard J Edmondson15, Michael Friedlander16. 1. The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom. Electronic address: susana.banerjee@rmh.nhs.uk. 2. NHMRC Clinical Trials Centre, University of Sydney, NSW 2050, Australia. 3. The Christie NHS Foundation Trust and University of Manchester, Manchester, United Kingdom. 4. Queen Elizabeth University Hospital, Glasgow, Scotland, United Kingdom. 5. The National Cancer Research Institute and the Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom. 6. Guys' and St Thomas' NHS Foundation Trust, London, United Kingdom. 7. Mount Vernon Cancer Centre, Middlesex, United Kingdom. 8. Cancer Research UK Edinburgh Centre, MRC IGMM, University of Edinburgh, Edinburgh, United Kingdom. 9. Calvary Mater Hospital, Newcastle, NSW 2298, Australia. 10. Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia. 11. Christchurch Women's Hospital, Christchurch, New Zealand. 12. Mercy Hospital for Women, Melbourne, VIC 3084, Australia. 13. Royal Women's Hospital, Melbourne, VIC 3052, Australia. 14. Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, United Kingdom. 15. Manchester Academic Health Science Centre, St Mary's Hospital, Manchester, United Kingdom. 16. Prince of Wales Clinical School UNSW and Royal Hospital for Women, Sydney, NSW 2031, Australia.
Abstract
BACKGROUND: Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs. METHODS: 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity. RESULTS: The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5-13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5-13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%-24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade. CONCLUSIONS: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs.
BACKGROUND: Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs. METHODS: 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity. RESULTS: The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5-13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5-13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%-24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade. CONCLUSIONS: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs.
Authors: Ignace Vergote; Antonio Gonzalez-Martin; Domenica Lorusso; Charlie Gourley; Mansoor Raza Mirza; Jean-Emmanuel Kurtz; Aikou Okamoto; Kathleen Moore; Frédéric Kridelka; Iain McNeish; Alexander Reuss; Bénédicte Votan; Andreas du Bois; Sven Mahner; Isabelle Ray-Coquard; Elise C Kohn; Jonathan S Berek; David S P Tan; Nicoletta Colombo; Rongyu Zang; Nicole Concin; Dearbhaile O'Donnell; Alejandro Rauh-Hain; C Simon Herrington; Christian Marth; Andres Poveda; Keiichi Fujiwara; Gavin C E Stuart; Amit M Oza; Michael A Bookman Journal: Lancet Oncol Date: 2022-08 Impact factor: 54.433